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Find video protocols related to scientific articles indexed in Pubmed.
Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Christopher J L Murray, Katrina F Ortblad, Caterina Guinovart, Stephen S Lim, Timothy M Wolock, D Allen Roberts, Emily A Dansereau, Nicholas Graetz, Ryan M Barber, Jonathan C Brown, Haidong Wang, Herbert C Duber, Mohsen Naghavi, Daniel Dicker, Lalit Dandona, Joshua A Salomon, Kyle R Heuton, Kyle Foreman, David E Phillips, Thomas D Fleming, Abraham D Flaxman, Bryan K Phillips, Elizabeth K Johnson, Megan S Coggeshall, Foad Abd-Allah, Semaw Ferede Abera, Jerry P Abraham, Ibrahim Abubakar, Laith J Abu-Raddad, Niveen Me Abu-Rmeileh, Tom Achoki, Austine Olufemi Adeyemo, Arsène Kouablan Adou, José C Adsuar, Emilie Elisabet Agardh, Dickens Akena, Mazin J Al Kahbouri, Deena Alasfoor, Mohammed I Albittar, Gabriel Alcalá-Cerra, Miguel Angel Alegretti, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, François Alla, Peter J Allen, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Benjamin O Anderson, Carl Abelardo T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Amitava Banerjee, Sanjay Basu, Justin Beardsley, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku Jibat Beyene, Neeraj Bhala, Ashish Bhalla, Zulfiqar A Bhutta, Aref Bin Abdulhak, Agnes Binagwaho, Jed D Blore, Berrak Bora Basara, Dipan Bose, Michael Brainin, Nicholas Breitborde, Carlos A Castañeda-Orjuela, Ferrán Catalá-López, Vineet K Chadha, Jung-Chen Chang, Peggy Pei-Chia Chiang, Ting-Wu Chuang, Mercedes Colomar, Leslie Trumbull Cooper, Cyrus Cooper, Karen J Courville, Benjamin C Cowie, Michael H Criqui, Rakhi Dandona, Anand Dayama, Diego De Leo, Louisa Degenhardt, Borja del Pozo-Cruz, Kebede Deribe, Don C Des Jarlais, Muluken Dessalegn, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Tim R Driscoll, Adnan M Durrani, Richard G Ellenbogen, Sergey Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Seyed-Mohammad Fereshtehnejad, Daniel Obadare Fijabi, Mohammad H Forouzanfar, Urbano Fra Paleo, Lynne Gaffikin, Amiran Gamkrelidze, Fortuné Gbètoho Gankpé, Johanna M Geleijnse, Bradford D Gessner, Katherine B Gibney, Ibrahim Abdelmageem Mohamed Ginawi, Elizabeth L Glaser, Philimon Gona, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rajeev Gupta, Rahul Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Josep Maria Haro, Rasmus Havmoeller, Simon I Hay, Mohammad T Hedayati, Ileana B Heredia Pi, Hans W Hoek, John C Hornberger, H Dean Hosgood, Peter J Hotez, Damian G Hoy, John J Huang, Kim M Iburg, Bulat T Idrisov, Kaire Innos, Kathryn H Jacobsen, Panniyammakal Jeemon, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Haidong Kan, Ida Kankindi, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Andre Keren, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Irma Khonelidze, Yohannes Kinfu, Jonas M Kinge, Luke Knibbs, Yoshihiro Kokubo, S Kosen, Barthélemy Kuate Defo, Veena S Kulkarni, Chanda Kulkarni, Kaushalendra Kumar, Ravi B Kumar, G Anil Kumar, Gene F Kwan, Taavi Lai, Arjun Lakshmana Balaji, Hilton Lam, Qing Lan, Van C Lansingh, Heidi J Larson, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Yichong Li, Yongmei Li, Graça Maria Ferreira De Lima, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Paulo A Lotufo, Vasco Manuel Pedro Machado, Jennifer H MacLachlan, Carlos Magis-Rodríguez, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Joseph R Masci, Mohammad Taufiq Mashal, Amanda J Mason-Jones, Bongani M Mayosi, Tasara T Mazorodze, Abigail Cecilia Mckay, Peter A Meaney, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Yohannes Adama Melaku, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Karzan Abdulmuhsin Mohammad, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Marcella Montico, Ami R Moore, Rintaro Mori, Wilkister Nyaora Moturi, Mitsuru Mukaigawara, Kinnari S Murthy, Aliya Naheed, Kovin S Naidoo, Luigi Naldi, Vinay Nangia, K M Venkat Narayan, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Vincent Nowaseb, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Aslam Pervaiz, Konrad Pesudovs, Max Petzold, Farshad Pourmalek, Dima Qato, Amado D Quezada, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Homie Razavi, Robert Quentin Reilly, Giuseppe Remuzzi, Jan Hendrik Richardus, Luca Ronfani, Nobhojit Roy, Nsanzimana Sabin, Mohammad Yahya Saeedi, Mohammad Ali Sahraian, Genesis May J Samonte, Monika Sawhney, Ione J C Schneider, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Rupak Shivakoti, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Edgar P Simard, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Samir Soneji, Sergey S Soshnikov, Chandrashekhar T Sreeramareddy, Vasiliki Kalliopi Stathopoulou, Konstantinos Stroumpoulis, Soumya Swaminathan, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Alan J Thomson, Andrew L Thorne-Lyman, Jeffrey A Towbin, Jefferson Traebert, Bach X Tran, Zacharie Tsala Dimbuene, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Selen Begüm Uzun, Andrew J Vallely, Tommi J Vasankari, N Venketasubramanian, Francesco S Violante, Vasiliy Victorovich Vlassov, Stein Emil Vollset, Stephen Waller, Mitchell T Wallin, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, Richard A White, James D Wilkinson, Thomas Neil Williams, Solomon Meseret Woldeyohannes, John Q Wong, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Theo Vos.
Lancet
PUBLISHED: 07-22-2014
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The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.
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Role of GSH homeostasis under Zn toxicity in plants with different Zn tolerance.
Plant Sci.
PUBLISHED: 06-23-2014
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Tripepthide glutathione (GSH) is a pivotal molecule in tolerance to heavy metals, including Zinc (Zn). The aim of our work is to examine the role of GSH metabolism in two different horticultural plants under Zn toxicity in order to select and/or generate plants tolerant to Zn toxicity. We show a comparative analysis of the toxic effect of 0.5mM Zn between Lactuca sativa cv. Phillipus and Brassica oleracea cv. Bronco. In L. sativa the accumulation of Zn resulted in an increase in reactive oxygen species (ROS), while enzymes of GSH metabolism and the activities of the antioxidant enzymes were negatively affected. On the contrary, B. oleracea showed the existence of a detoxification mechanism of these ROS. Moreover, while in L. sativa increased the oxidized GSH (GSSG) and phytochelatins (PCs) concentration with the reduction of leaves biomass, in B. oleracea the higher concentration of reduced GSH and its use in the detoxification of ROS seems to be a major mechanism to provide tolerance to Zn toxicity without reducing leaf biomass. Our results suggested that under Zn toxicity, B. oleracea is more efficient and tolerant than L. sativa through the detoxification of lipid peroxidation products due to the reduced GSH.
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Global, regional, and national levels and causes of maternal mortality during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.
Nicholas J Kassebaum, Amelia Bertozzi-Villa, Megan S Coggeshall, Katya A Shackelford, Caitlyn Steiner, Kyle R Heuton, Diego Gonzalez-Medina, Ryan Barber, Chantal Huynh, Daniel Dicker, Tara Templin, Timothy M Wolock, Ayse Abbasoglu Ozgoren, Foad Abd-Allah, Semaw Ferede Abera, Ibrahim Abubakar, Tom Achoki, Ademola Adelekan, Zanfina Ademi, Arsène Kouablan Adou, José C Adsuar, Emilie E Agardh, Dickens Akena, Deena Alasfoor, Zewdie Aderaw Alemu, Rafael Alfonso-Cristancho, Samia Alhabib, Raghib Ali, Mazin J Al Kahbouri, François Alla, Peter J Allen, Mohammad A AlMazroa, Ubai Alsharif, Elena Alvarez, Nelson Alvis-Guzmán, Adansi A Amankwaa, Azmeraw T Amare, Hassan Amini, Walid Ammar, Carl A T Antonio, Palwasha Anwari, Johan Arnlöv, Valentina S Arsic Arsenijevic, Ali Artaman, Majed Masoud Asad, Rana J Asghar, Reza Assadi, Lydia S Atkins, Alaa Badawi, Kalpana Balakrishnan, Arindam Basu, Sanjay Basu, Justin Beardsley, Neeraj Bedi, Tolesa Bekele, Michelle L Bell, Eduardo Bernabé, Tariku J Beyene, Zulfiqar Bhutta, Aref Bin Abdulhak, Jed D Blore, Berrak Bora Basara, Dipan Bose, Nicholas Breitborde, Rosario Cárdenas, Carlos A Castañeda-Orjuela, Ruben Estanislao Castro, Ferrán Catalá-López, Alanur Cavlin, Jung-Chen Chang, Xuan Che, Costas A Christophi, Sumeet S Chugh, Massimo Cirillo, Samantha M Colquhoun, Leslie Trumbull Cooper, Cyrus Cooper, Iuri da Costa Leite, Lalit Dandona, Rakhi Dandona, Adrian Davis, Anand Dayama, Louisa Degenhardt, Diego De Leo, Borja del Pozo-Cruz, Kebede Deribe, Muluken Dessalegn, Gabrielle A deVeber, Samath D Dharmaratne, Ugur Dilmen, Eric L Ding, Rob E Dorrington, Tim R Driscoll, Sergei Petrovich Ermakov, Alireza Esteghamati, Emerito Jose A Faraon, Farshad Farzadfar, Manuela Mendonca Felicio, Seyed-Mohammad Fereshtehnejad, Graça Maria Ferreira De Lima, Mohammad H Forouzanfar, Elisabeth B França, Lynne Gaffikin, Ketevan Gambashidze, Fortuné Gbètoho Gankpé, Ana C Garcia, Johanna M Geleijnse, Katherine B Gibney, Maurice Giroud, Elizabeth L Glaser, Ketevan Goginashvili, Philimon Gona, Dinorah González-Castell, Atsushi Goto, Hebe N Gouda, Harish Chander Gugnani, Rahul Gupta, Rajeev Gupta, Nima Hafezi-Nejad, Randah Ribhi Hamadeh, Mouhanad Hammami, Graeme J Hankey, Hilda L Harb, Rasmus Havmoeller, Simon I Hay, Ileana B Heredia Pi, Hans W Hoek, H Dean Hosgood, Damian G Hoy, Abdullatif Husseini, Bulat T Idrisov, Kaire Innos, Manami Inoue, Kathryn H Jacobsen, Eiman Jahangir, Sun Ha Jee, Paul N Jensen, Vivekanand Jha, Guohong Jiang, Jost B Jonas, Knud Juel, Edmond Kato Kabagambe, Haidong Kan, Nadim E Karam, André Karch, Corine Kakizi Karema, Anil Kaul, Norito Kawakami, Konstantin Kazanjan, Dhruv S Kazi, Andrew H Kemp, André Pascal Kengne, Maia Kereselidze, Yousef Saleh Khader, Shams Eldin Ali Hassan Khalifa, Ejaz Ahmed Khan, Young-Ho Khang, Luke Knibbs, Yoshihiro Kokubo, Soewarta Kosen, Barthélemy Kuate Defo, Chanda Kulkarni, Veena S Kulkarni, G Anil Kumar, Kaushalendra Kumar, Ravi B Kumar, Gene Kwan, Taavi Lai, Ratilal Lalloo, Hilton Lam, Van C Lansingh, Anders Larsson, Jong-Tae Lee, James Leigh, Mall Leinsalu, Ricky Leung, Xiaohong Li, Yichong Li, Yongmei Li, Juan Liang, Xiaofeng Liang, Stephen S Lim, Hsien-Ho Lin, Steven E Lipshultz, Shiwei Liu, Yang Liu, Belinda K Lloyd, Stephanie J London, Paulo A Lotufo, Jixiang Ma, Stefan Ma, Vasco Manuel Pedro Machado, Nana Kwaku Mainoo, Marek Majdan, Christopher Chabila Mapoma, Wagner Marcenes, Melvin Barrientos Marzan, Amanda J Mason-Jones, Man Mohan Mehndiratta, Fabiola Mejia-Rodriguez, Ziad A Memish, Walter Mendoza, Ted R Miller, Edward J Mills, Ali H Mokdad, Glen Liddell Mola, Lorenzo Monasta, Jonathan de la Cruz Monis, Julio Cesar Montañez Hernandez, Ami R Moore, Maziar Moradi-Lakeh, Rintaro Mori, Ulrich O Mueller, Mitsuru Mukaigawara, Aliya Naheed, Kovin S Naidoo, Devina Nand, Vinay Nangia, Denis Nash, Chakib Nejjari, Robert G Nelson, Sudan Prasad Neupane, Charles R Newton, Marie Ng, Mark J Nieuwenhuijsen, Muhammad Imran Nisar, Sandra Nolte, Ole F Norheim, Luke Nyakarahuka, In-Hwan Oh, Takayoshi Ohkubo, Bolajoko O Olusanya, Saad B Omer, John Nelson Opio, Orish Ebere Orisakwe, Jeyaraj D Pandian, Christina Papachristou, Jae-Hyun Park, Angel J Paternina Caicedo, Scott B Patten, Vinod K Paul, Boris Igor Pavlin, Neil Pearce, David M Pereira, Konrad Pesudovs, Max Petzold, Dan Poenaru, Guilherme V Polanczyk, Suzanne Polinder, Dan Pope, Farshad Pourmalek, Dima Qato, D Alex Quistberg, Anwar Rafay, Kazem Rahimi, Vafa Rahimi-Movaghar, Sajjad Ur Rahman, Murugesan Raju, Saleem M Rana, Amany Refaat, Luca Ronfani, Nobhojit Roy, Tania Georgina Sánchez Pimienta, Mohammad Ali Sahraian, Joshua A Salomon, Uchechukwu Sampson, Itamar S Santos, Monika Sawhney, Felix Sayinzoga, Ione J C Schneider, Austin Schumacher, David C Schwebel, Soraya Seedat, Sadaf G Sepanlou, Edson E Servan-Mori, Marina Shakh-Nazarova, Sara Sheikhbahaei, Kenji Shibuya, Hwashin Hyun Shin, Ivy Shiue, Inga Dora Sigfusdottir, Donald H Silberberg, Andrea P Silva, Jasvinder A Singh, Vegard Skirbekk, Karen Sliwa, Sergey S Soshnikov, Luciano A Sposato, Chandrashekhar T Sreeramareddy, Konstantinos Stroumpoulis, Lela Sturua, Bryan L Sykes, Karen M Tabb, Roberto Tchio Talongwa, Feng Tan, Carolina Maria Teixeira, Eric Yeboah Tenkorang, Abdullah Sulieman Terkawi, Andrew L Thorne-Lyman, David L Tirschwell, Jeffrey A Towbin, Bach X Tran, Miltiadis Tsilimbaris, Uche S Uchendu, Kingsley N Ukwaja, Eduardo A Undurraga, Selen Begüm Uzun, Andrew J Vallely, Coen H van Gool, Tommi J Vasankari, Monica S Vavilala, N Venketasubramanian, Salvador Villalpando, Francesco S Violante, Vasiliy Victorovich Vlassov, Theo Vos, Stephen Waller, Haidong Wang, Linhong Wang, Xiaorong Wang, Yanping Wang, Scott Weichenthal, Elisabete Weiderpass, Robert G Weintraub, Ronny Westerman, James D Wilkinson, Solomon Meseret Woldeyohannes, John Q Wong, Muluemebet Abera Wordofa, Gelin Xu, Yang C Yang, Yuichiro Yano, Gokalp Kadri Yentur, Paul Yip, Naohiro Yonemoto, Seok-Jun Yoon, Mustafa Z Younis, Chuanhua Yu, Kim Yun Jin, Maysaa El Sayed Zaki, Yong Zhao, Yingfeng Zheng, Maigeng Zhou, Jun Zhu, Xiao Nong Zou, Alan D Lopez, Mohsen Naghavi, Christopher J L Murray, Rafael Lozano.
Lancet
PUBLISHED: 05-02-2014
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The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100,000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.
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Amitriptyline reverses hyperalgesia and improves associated mood-like disorders in a model of experimental monoarthritis.
Behav. Brain Res.
PUBLISHED: 01-29-2014
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Affective disorders are common comorbidities of chronic inflammatory pain that are often overlooked in primary care. As the impact of inflammatory pain upon mood-like disorders in animal models is not well known, our objective was to assess whether prolonged experimental monoarthritis (ARTH) induced the development of anxiety and depressive-like behaviours in rodents and if amitriptyline, an antidepressant commonly used in the treatment of chronic pain, could reverse both nociceptive and mood-like impairments. Experimental ARTH was induced through an injection of kaolin/carrageenan into the right knee joint with control (SHAM) animals injected with saline. Four weeks after induction, ARTH animals displayed mechanical hyperalgesia and a depressive-like phenotype as they showed a significant increase in immobility and a decrease in the latency to immobility in the forced-swimming test at the expense of the time spent climbing/swimming. ARTH animals also displayed a decreased sucrose preference, an index of anhedonia and anxiety-like behaviour as time spent exploring the open arms of the elevated-plus-maze was decreased when compared to controls. The anxiety-like phenotype was also supported by an increase in the number of fecal boli left in the open field. In ARTH animals, the administration of amitriptyline decreased mechanical hyperalgesia and increased sucrose preference and the time spent climbing, although it had a deleterious effect in the performance of control animals. Our data show that this model of ARTH can be useful for the study of chronic pain-mood disorders comorbidities and that amitriptyline is able to partly reverse the associated nociceptive and emotional impairments.
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A Role of Supraspinal Galanin in Behavioural Hyperalgesia in the Rat.
PLoS ONE
PUBLISHED: 01-01-2014
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In chronic pain disorders, galanin (GAL) is able to either facilitate or inhibit nociception in the spinal cord but the contribution of supraspinal galanin to pain signalling is mostly unknown. The dorsomedial nucleus of the hypothalamus (DMH) is rich in galanin receptors (GALR) and is involved in behavioural hyperalgesia. In this study, we evaluated the contribution of supraspinal GAL to behavioural hyperalgesia in experimental monoarthritis.
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Anti-inflammatory effect of unsaturated fatty acids and Ergosta-7,22-dien-3-ol from Marthasterias glacialis: prevention of CHOP-mediated ER-stress and NF-?B activation.
PLoS ONE
PUBLISHED: 01-01-2014
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There has been increasing awareness to the potential interest of drug discovery from marine natural products to treat several pathological conditions, including inflammation. In this work we describe the anti-inflammatory activity of several compounds present in the echinoderm Marthasterias glacialis (spiny sea-star), using the inflammatory model RAW 264.7 cells challenged with LPS. Lipidomic profiling of the organism revealed two major classes of compounds: fatty acids and sterols. Among these, the predominant compounds cis 11-eicosenoic and cis 11,14 eicosadienoic acids and the unsaturated sterol ergosta-7,22-dien-3-ol were evaluated. The mechanism of action of the compounds was distinct as they modulated different levels of the inflammation pathway. Classical inflammatory markers, such as COX-2, iNOS, IL-6 and NF-?B, were evaluated. We also studied the contribution of the CHOP pathway-mediated ER-stress to the inflammatory process. Overall, the sterol ergosta-7,22-dien-3-ol was the most active compound, however maximum activity was obtained when all compounds were tested in combination, thus suggesting a potentially synergistic activity of both classes of metabolites. This work establishes the echinoderm M. glacialis as an interesting source of anti-inflammatory molecules.
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Palmitic Acid and Ergosta-7,22-dien-3-ol Contribute to the Apoptotic Effect and Cell Cycle Arrest of an Extract from Marthasterias glacialis L. in Neuroblastoma Cells.
Mar Drugs
PUBLISHED: 10-18-2013
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We describe the effect of a chemically characterized lipophilic extract obtained from Marthasterias glacialis L. against human breast cancer (MCF-7) and human neuroblastoma (SH-SY5Y) cell lines. Evaluation of DNA synthesis revealed that both cell lines were markedly affected in a concentration-dependent way, the SH-SY5Y cell line being more susceptible. Cell cycle arrest was observed, an effect induced by the sterol, ergosta-7,22-dien-3-ol, present in the extract. Morphological evaluation of treated cells showed the advent of lipid droplets and chromatin condensation compatible with apoptosis, which was confirmed by the evaluation of caspase-3 and -9 activities. Palmitic acid was the main compound responsible for this apoptotic effect by a ceramide-independent mechanism that involved endoplasmic reticulum (ER)-stress with upregulation of CCAAT/-enhancer-binding protein homologous protein (CHOP).
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Modeling Mass Transfer from Carmustine-Loaded Polymeric Implants for Malignant Gliomas.
J Lab Autom
PUBLISHED: 08-23-2013
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Significant advances in the encapsulation and release of drugs from degradable polymers have led to the Food and Drug Administration approval of Gliadel wafers for controlled local delivery of the chemotherapeutic drug carmustine to high-grade gliomas following surgical resection. Due to the localized nature of the delivery method, no pharmacokinetic measurements have been taken in humans. Rather, pharmacokinetic studies in animals and associated modeling have indicated the capability of carmustine to be delivered in high concentrations within millimeters from the implant site over approximately 5 days. Mathematical models have indicated that diffusion has a primary role in transport, which may be complemented by enhanced fluid convection from postsurgical edema in the initial 3 days following implantation. Carmustines penetration distance is also presumably limited by its lipophilicity and permeability in the capillaries. This review discusses the mathematical models that have been used to predict the release and distribution of carmustine from a polymeric implant. These models provide a theoretical framework for greater understanding of systems for localized drug delivery while highlighting factors that should be considered in clinical applications. In effect, Gliadel wafers and similar drug delivery implants can be optimized with reduction in required time and resources with such a quantitative and integrative approach.
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A drug information center module to train pharmacy students in evidence-based practice.
Am J Pharm Educ
PUBLISHED: 05-30-2013
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To use a drug information center training module to teach evidence-based medicine to pharmacy students and to assess their satisfaction with the experience.
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Pronociception from the dorsomedial nucleus of the hypothalamus is mediated by the rostral ventromedial medulla in healthy controls but is absent in arthritic animals.
Brain Res. Bull.
PUBLISHED: 04-16-2013
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The dorsomedial nucleus of the hypothalamus (DMH) has been proposed to participate in stress-induced hyperalgesia through facilitation of pronociceptive cells in the rostroventromedial medulla (RVM). We hypothesized that the DMH participates in hyperalgesia induced by arthritis. The DMH was pharmacologically manipulated while assessing heat-evoked nociceptive behavior or the discharge rates of pronociceptive RVM ON- and antinociceptive RVM OFF-like cells in NAIVE, SHAM and monoarthritic (ARTH) animals. In NAIVE and SHAM animals, the changes in nociceptive behavior induced by activation of the DMH by glutamate and inhibition by lidocaine were in line with earlier evidence indicating that the DMH has a nociceptive facilitating role. However, in ARTH animals, neither activation nor inhibition of the DMH influenced pain-like behavior evoked by stimulation of an uninflamed skin region (paw and tail). In accordance with these behavioral results, activation or inhibition of the DMH induced pronociceptive changes in the discharge rates of RVM cells in NAIVE and SHAM animals, which suggests that the DMH has a pronociceptive role mediated by the RVM in normal animals. However, in ARTH animals, both glutamate and lidocaine in the DMH failed to influence either pain-like behavior or noxious stimulation-evoked responses of RVM cells, while blocking the DMH increased spontaneous activity in the pronociceptive RVM ON cells. Our data indicate that the DMH participates in descending facilitation of cutaneous nociception in healthy controls, but it is not engaged in the regulation of cutaneous nociception in monoarthritic animals, while a minor role in tonic suppression of nociception in arthritis cannot be discarded.
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Is characterizing the digital forensic facial reconstruction with hair necessary? A familiar assessors analysis.
Forensic Sci. Int.
PUBLISHED: 02-12-2013
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In the international scientific literature, there are few studies that emphasize the presence or absence of hair in forensic facial reconstructions. There are neither Brazilian studies concerning digital facial reconstructions without hair, nor research comparing recognition tests between digital facial reconstructions with hair and without hair. The miscegenation of Brazilian people is considerable. Brazilian people, and, in particular, Brazilian women, even if considered as Caucasoid, may present the hair in very different ways: curly, wavy or straight, blonde, red, brown or black, long or short, etc. For this reason, it is difficult to find a correct type of hair for facial reconstruction (unless, in real cases, some hair is recovered with the skeletal remains).
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Amino acids, fatty acids and sterols profile of some marine organisms from Portuguese waters.
Food Chem
PUBLISHED: 01-17-2013
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Marine organisms have been increasingly regarded as good sources of new drugs for human therapeutics and also as nutrients for human diet. The amino acids, fatty acids and sterols profiles of the widely consumed echinoderms Paracentrotus lividus Lamarck (sea urchin), Holothuria forskali Chiaje (sea cucumber), the gastropod molluscs Aplysia fasciata Poiret and Aplysia punctata Cuvier (sea hares), from Portuguese waters, were established by GC-MS analysis. Overall, 10 amino acids, 14 fatty acids and 4 sterols were determined. In general, all species presented the 10 amino acids identified, with the exceptions of H. forskali, in which no glycine, proline, trans-4-hydroxy-proline or phenylalanine were found, and of A. fasciata which did not contain proline. Unsaturated fatty acids were predominant compounds, with those from the ?-6 series, being in higher amounts than their ?-3 homologues, and cholesterol being the main sterol. The amino acids, fatty acids and sterols qualitative and quantitative composition of A. fasciata, A. punctata and H. forskali is reported here for the first time.
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Investment into Defensive Traits by Anuran Prey (Lithobates pipiens) Is Mediated by the Starvation-Predation Risk Trade-Off.
PLoS ONE
PUBLISHED: 01-01-2013
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Prey can invest in a variety of defensive traits when balancing risk of predation against that of starvation. What remains unknown is the relative costs of different defensive traits and how prey reconcile investment into these traits when energetically limited. We tested the simple allocation model of prey defense, which predicts an additive effect of increasing predation risk and resource availability, resulting in the full deployment of defensive traits under conditions of high risk and resource saturation. We collected morphometric, developmental, and behavioural data in an experiment using dragonfly larvae (predator) and Northern leopard frog tadpoles (prey) subject to variable levels of food availability and predation risk. Larvae exposed to food restriction showed limited response to predation risk; larvae at food saturation altered behaviour, development, and growth in response to predation risk. Responses to risk varied through time, suggesting ontogeny may affect the deployment of particular defensive traits. The observed negative correlation between body size and activity level for food-restricted prey - and the absence of a similar response among adequately-fed prey - suggests that a trade-off exists between behavioural and growth responses when energy budgets are limited. Our research is the first to demonstrate how investment into these defensive traits is mediated along gradients of both predation risk and resource availability over time. The interactions we demonstrate between resource availability and risk level on deployment of inducible defenses provide evidence that both internal condition and extrinsic risk factors play a critical role in the production of inducible defenses over time.
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Neudesin is involved in anxiety behavior: structural and neurochemical correlates.
Front Behav Neurosci
PUBLISHED: 01-01-2013
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Neudesin (also known as neuron derived neurotrophic factor, Nenf) is a scarcely studied putative non-canonical neurotrophic factor. In order to understand its function in the brain, we performed an extensive behavioral characterization (motor, emotional, and cognitive dimensions) of neudesin-null mice. The absence of neudesin leads to an anxious-like behavior as assessed in the elevated plus maze (EPM), light/dark box (LDB) and novelty suppressed feeding (NSF) tests, but not in the acoustic startle (AS) test. This anxious phenotype is associated with reduced dopaminergic input and impoverished dendritic arborizations in the dentate gyrus granule neurons of the ventral hippocampus. Interestingly, shorter dendrites are also observed in the bed nucleus of the stria terminalis (BNST) of neudesin-null mice. These findings lead us to suggest that neudesin is a novel relevant player in the maintenance of the anxiety circuitry.
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Tests of one Brazilian facial reconstruction method using three soft tissue depth sets and familiar assessors.
Forensic Sci. Int.
PUBLISHED: 07-28-2011
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Facial reconstruction is a method that seeks to recreate a persons facial appearance from his/her skull. This technique can be the last resource used in a forensic investigation, when identification techniques such as DNA analysis, dental records, fingerprints and radiographic comparison cannot be used to identify a body or skeletal remains. To perform facial reconstruction, the data of facial soft tissue thickness are necessary. Scientific literature has described differences in the thickness of facial soft tissue between ethnic groups. There are different databases of soft tissue thickness published in the scientific literature. There are no literature records of facial reconstruction works carried out with data of soft tissues obtained from samples of Brazilian subjects. There are also no reports of digital forensic facial reconstruction performed in Brazil. There are two databases of soft tissue thickness published for the Brazilian population: one obtained from measurements performed in fresh cadavers (fresh cadavers pattern), and another from measurements using magnetic resonance imaging (Magnetic Resonance pattern). This study aims to perform three different characterized digital forensic facial reconstructions (with hair, eyelashes and eyebrows) of a Brazilian subject (based on an international pattern and two Brazilian patterns for soft facial tissue thickness), and evaluate the digital forensic facial reconstructions comparing them to photos of the individual and other nine subjects. The DICOM data of the Computed Tomography (CT) donated by a volunteer were converted into stereolitography (STL) files and used for the creation of the digital facial reconstructions. Once the three reconstructions were performed, they were compared to photographs of the subject who had the face reconstructed and nine other subjects. Thirty examiners participated in this recognition process. The target subject was recognized by 26.67% of the examiners in the reconstruction performed with the Brazilian Magnetic Resonance Pattern, 23.33% in the reconstruction performed with the Brazilian Fresh Cadavers Pattern and 20.00% in the reconstruction performed with the International Pattern, in which the target-subject was the most recognized subject in the first two patterns. The rate of correct recognitions of the target subject indicate that the digital forensic facial reconstruction, conducted with parameters used in this study, may be a useful tool.
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New Markov-Shannon Entropy models to assess connectivity quality in complex networks: from molecular to cellular pathway, Parasite-Host, Neural, Industry, and Legal-Social networks.
J. Theor. Biol.
PUBLISHED: 07-22-2011
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Graph and Complex Network theory is expanding its application to different levels of matter organization such as molecular, biological, technological, and social networks. A network is a set of items, usually called nodes, with connections between them, which are called links or edges. There are many different experimental and/or theoretical methods to assign node-node links depending on the type of network we want to construct. Unfortunately, the use of a method for experimental reevaluation of the entire network is very expensive in terms of time and resources; thus the development of cheaper theoretical methods is of major importance. In addition, different methods to link nodes in the same type of network are not totally accurate in such a way that they do not always coincide. In this sense, the development of computational methods useful to evaluate connectivity quality in complex networks (a posteriori of network assemble) is a goal of major interest. In this work, we report for the first time a new method to calculate numerical quality scores S(L(ij)) for network links L(ij) (connectivity) based on the Markov-Shannon Entropy indices of order k-th (?(k)) for network nodes. The algorithm may be summarized as follows: (i) first, the ?(k)(j) values are calculated for all j-th nodes in a complex network already constructed; (ii) A Linear Discriminant Analysis (LDA) is used to seek a linear equation that discriminates connected or linked (L(ij)=1) pairs of nodes experimentally confirmed from non-linked ones (L(ij)=0); (iii) the new model is validated with external series of pairs of nodes; (iv) the equation obtained is used to re-evaluate the connectivity quality of the network, connecting/disconnecting nodes based on the quality scores calculated with the new connectivity function. This method was used to study different types of large networks. The linear models obtained produced the following results in terms of overall accuracy for network reconstruction: Metabolic networks (72.3%), Parasite-Host networks (93.3%), CoCoMac brain cortex co-activation network (89.6%), NW Spain fasciolosis spreading network (97.2%), Spanish financial law network (89.9%) and World trade network for Intelligent & Active Food Packaging (92.8%). In order to seek these models, we studied an average of 55,388 pairs of nodes in each model and a total of 332,326 pairs of nodes in all models. Finally, this method was used to solve a more complicated problem. A model was developed to score the connectivity quality in the Drug-Target network of US FDA approved drugs. In this last model the ?(k) values were calculated for three types of molecular networks representing different levels of organization: drug molecular graphs (atom-atom bonds), protein residue networks (amino acid interactions), and drug-target network (compound-protein binding). The overall accuracy of this model was 76.3%. This work opens a new door to the computational reevaluation of network connectivity quality (collation) for complex systems in molecular, biomedical, technological, and legal-social sciences as well as in world trade and industry.
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Efforts to support the development of fusidic acid in the United States.
Clin. Infect. Dis.
PUBLISHED: 05-07-2011
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Fusidic acid (FA), though used widely throughout the world for decades, has never been approved in the United States. There is now a great need for an oral methicillin-resistant Staphylococcus aureus (MRSA) antibiotic with a long track record of safety. Cempra Pharmaceuticals successfully encouraged passage of a congressional amendment to allow for Hatch-Waxman market exclusivity when this antibiotic is approved in the United States. A new dosing regimen has been patented, allowing FA to be used as monotherapy, and decreased resistance selectivity has been shown. With almost no resistance to FA in the United States, the time is right for introduction into this market.
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Anti-proliferative activity of meroditerpenoids isolated from the brown alga Stypopodium flabelliforme against several cancer cell lines.
Mar Drugs
PUBLISHED: 03-29-2011
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The sea constitutes one of the most promising sources of novel compounds with potential application in human therapeutics. In particular, algae have proved to be an interesting source of new bioactive compounds. In this work, six meroditerpenoids (epitaondiol, epitaondiol diacetate, epitaondiol monoacetate, stypotriol triacetate, 14-ketostypodiol diacetate and stypodiol) isolated from the brown alga Stypopodium flabelliforme were tested for their cell proliferation inhibitory activity in five cell lines. Cell lines tested included human colon adenocarcinoma (Caco-2), human neuroblastoma (SH-SY5Y), rat basophilic leukemia (RBL-2H3), murine macrophages (RAW.267) and Chinese hamster fibroblasts (V79). Antimicrobial activity of the compounds was also evaluated against Staphylococcus aureus, Salmonella typhimurium, Proteus mirabilis, Bacillus cereus, Enterococcus faecalis and Micrococcus luteus. Overall, the compounds showed good activity against all cell lines, with SH-SY5Y and RAW.267 being the most susceptible. Antimicrobial capacity was observed for epitaondiol monoacetate, stypotriol triacetate and stypodiol, with the first being the most active. The results suggest that these molecules deserve further studies in order to evaluate their potential as therapeutic agents.
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Identification of phenolic compounds in isolated vacuoles of the medicinal plant Catharanthus roseus and their interaction with vacuolar class III peroxidase: an H?O? affair?
J. Exp. Bot.
PUBLISHED: 02-28-2011
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Class III peroxidases (Prxs) are plant enzymes capable of using H(2)O(2) to oxidize a range of plant secondary metabolites, notably phenolic compounds. These enzymes are localized in the cell wall or in the vacuole, which is a target for secondary metabolite accumulation, but very little is known about the function of vacuolar Prxs. Here, the physiological role of the main leaf vacuolar Prx of the medicinal plant Catharanthus roseus, CrPrx1, was further investigated namely by studying its capacity to oxidize co-localized phenolic substrates at the expense of H(2)O(2). LC-PAD-MS analysis of the phenols from isolated leaf vacuoles detected the presence of three caffeoylquinic acids and four flavonoids in this organelle. These phenols or similar compounds were shown to be good CrPrx1 substrates, and the CrPrx1-mediated oxidation of 5-O-caffeoylquinic acid was shown to form a co-operative regenerating cycle with ascorbic acid. Interestingly, more than 90% of total leaf Prx activity was localized in the vacuoles, associated to discrete spots of the tonoplast. Prx activity inside the vacuoles was estimated to be 1809 nkat ml(-1), which, together with the determined concentrations for the putative vacuolar phenolic substrates, indicate a very high H(2)O(2) scavenging capacity, up to 9 mM s(-1). Accordingly, high light conditions, known to increase H(2)O(2) production, induced both phenols and Prx levels. Therefore, it is proposed that the vacuolar couple Prx/secondary metabolites represent an important sink/buffer of H(2)O(2) in green plant cells.
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Antioxidants from barley husks impregnated in films of low-density polyethylene and their effect over lipid deterioration of frozen cod (Gadus morhua).
J. Sci. Food Agric.
PUBLISHED: 02-02-2011
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The changes in quality of cod fillets packaged in films with and without antioxidants during 12 months of frozen storage at - 20 °C were investigated in the present study. The following parameters were determined in order to study lipid hydrolysis and primary and secondary lipid oxidation in the samples during frozen storage: peroxide value, conjugated dienes, conjugated triene hydroperoxides, free fatty acids, totox value, thiobarbituric acid-reactive substances and p-anisidine value.
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Real-time single-cell response to stiffness.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 09-07-2010
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Living cells adapt to the stiffness of their environment. However, cell response to stiffness is mainly thought to be initiated by the deformation of adhesion complexes under applied force. In order to determine whether cell response was triggered by stiffness or force, we have developed a unique method allowing us to tune, in real time, the effective stiffness experienced by a single living cell in a uniaxial traction geometry. In these conditions, the rate of traction force buildup dF/dt was adapted to stiffness in less than 0.1 s. This integrated fast response was unambiguously triggered by stiffness, and not by force. It suggests that early cell response could be mechanical in nature. In fact, local force-dependent signaling through adhesion complexes could be triggered and coordinated by the instantaneous cell-scale adaptation of dF/dt to stiffness. Remarkably, the effective stiffness method presented here can be implemented on any mechanical setup. Thus, beyond single-cell mechanosensing, this method should be useful to determine the role of rigidity in many fundamental phenomena such as morphogenesis and development.
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Synthesis and antibacterial activity of novel 4-aryl-[1,2,3]-triazole containing macrolides.
Bioorg. Med. Chem. Lett.
PUBLISHED: 08-27-2010
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Two series of novel triazole containing 14-member macrolides having either a cladinose or a 3-pyridyl acetate group at the 3-position of the macrolide ring were synthesized. The in vitro antibacterial activities against S. aureus, S. pneumoniae, S. pyogenes and E. faecalis were determined. Macrolide 7a and the fluoroketolide 1 (CEM-101) were evaluated in vivo in murine systemic infection models. All of the macrolide analogs were less active in vitro and in vivo than the fluoroketolide 1 (CEM-101).
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HPLC-PAD-atmospheric pressure chemical ionization-MS metabolite profiling of cytotoxic carotenoids from the echinoderm Marthasterias glacialis (spiny sea-star).
J Sep Sci
PUBLISHED: 06-25-2010
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An HPLC-PAD-atmospheric pressure chemical ionization-MS metabolite profiling analysis was conducted on the marine echinoderm Marthasterias glacialis (spiny sea-star). Bio-guided purification of the methanolic extract led to the isolation of several carotenoids, namely zeaxanthin, astaxanthin and lutein. These compounds were characterized using both UV-Vis characteristics and MS spectra interpretation. No previous works addressed the MS analysis of carotenoids present in this organism. The purified carotenoid fraction displayed a strong cell proliferation inhibition against rat basophilic leukemia RBL-2H3 (IC(25)=268 microg/mL) cancer cell line. Against healthy V79 (rat lung fibroblasts (IC(25)=411 microg/mL)) cell line, however, toxicity was lower, as it is desired for anti-cancer molecules. This study suggests that M. glacialis may constitute a good source of bioactive compounds that can be used as lead compounds for the pharmaceutical industry.
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First report of non-coloured flavonoids in Echium plantagineum bee pollen: differentiation of isomers by liquid chromatography/ion trap mass spectrometry.
Rapid Commun. Mass Spectrom.
PUBLISHED: 02-27-2010
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Apicultural products have been widely used in diet complements as well as in phytotherapy. Bee pollen from Echium plantagineum was analysed by high-performance liquid chromatography/photodiode-array detection coupled to ion trap mass spectrometry (HPLC-PAD-MS(n)) with an electrospray ionisation interface. The structures have been determined by the study of the ion mass fragmentation, which characterises the interglycosidic linkage in glycosylated flavonoids and differentiates positional isomers. Twelve non-coloured flavonoids were characterised, being kaempferol-3-O-neohesperidoside the major compound, besides others in trace amounts. These include quercetin, kaempferol and isorhamnetin glycosides, with several of them being isomers. Acetylated derivatives are also described. This is the first time that non-coloured flavonoids are reported from this pollen, with MS fragmentation proving to be most useful in the elucidation of isomeric structures.
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Tomato ( Lycopersicon esculentum ) seeds: new flavonols and cytotoxic effect.
J. Agric. Food Chem.
PUBLISHED: 02-06-2010
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In this study, seeds of Lycopersicon esculentum Mill. were analyzed by HPLC/UV-PAD/MS(n)-ESI. Fourteen flavonoids were identified, including quercetin, kaempferol, and isorhamnetin derivatives, with 13 of them being reported for the first time in tomato seeds. The major identified compounds were quercetin-3-O-sophoroside, kaempferol-3-O-sophoroside, and isorhamnetin-3-O-sophoroside. A significant cell proliferation inhibition (>80%), against rat basophile leukemia (RBL-2H3) cell line, was observed with this extract (IC(50) = 5980 microg/mL). For acetylcholinesterase inhibitory activity, a concentration-dependent effect was verified (IC(20) = 2400 microg/mL). The same behavior was noted regarding antioxidant capacity, evaluated against DPPH (IC(10) = 284 microg/mL), nitric oxide (IC(25) = 396 microg/L), and superoxide radicals (IC(25) = 3 microg/mL).
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Phenolics metabolism in insects: Pieris brassicae-Brassica oleracea var. costata ecological duo.
J. Agric. Food Chem.
PUBLISHED: 09-22-2009
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Changes in the phenolics composition of Pieris brassicae larvae fasted for distinct periods (1, 2, 4, 6, and 8 h) and their excrements and of Brassica oleracea L. var. costata DC leaves were determined by high-pressure liquid chromatography/UV-photo diode array detector/mass spectrometry-electrospray ionization. This is the first report following phenolics metabolism by P. brassicae through time. The results evidence that P. brassicae sequesters and metabolizes the phenolic compounds from the host plant. In a general way, deacylation was the main metabolic reaction that took place, but deglycosylation and sulfate conjugation reactions also occur. Additionally, several kaempferol derivatives containing rhamnose, which is not common in Brassica, were found in the host plant. Attending to the bioactivities recognized for the type of identified compounds, the different materials may constitute an interesting source of bioactive compounds, namely, of highly glycosylated and acylated kaempferol and quercetin derivatives, constituting an economic advantage for producers who have great losses caused by this pest. In addition, a deeper understanding of phenolics metabolism in insects was pursued.
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Discourses of anxiety and transference in nursing practice: the subject of knowledge.
Nurs Inq
PUBLISHED: 08-20-2009
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The nurses relationship to knowledge has been theorised in a variety of different ways, not the least being in relation to medical dominance. In this study, the authors report on one of the findings of a case study into nurses anxiety informed by psychoanalytic theory. They argue that the nurses subjection to the knowledge of the other health professional, inclusive of the doctor, can be a transference arising in the context of anxiety for the nurse. Grasped by anxiety, the nurse finds their own knowledge insufficient and in this moment can operate a transference to their non-nursing colleague, who obligingly, responds. This transference is not present in the change-of-shift handover report though, when the others knowledge is suspect, even open to derision. Thus, this reference to the knowledge of the other is not consistently present in nursing and can be seen to be just one way that nurses organise themselves in relation to anxiety. Therefore, those wanting to break down the medical dominance of the nursing profession might consider other ways nurses might organise themselves in relation to anxiety, so that the political dominance of the other is not reinforced via transference to that other.
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Pharmacological effects of Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission.
Phytomedicine
PUBLISHED: 08-01-2009
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The leaves of Catharanthus roseus constitute the only source of the well known indolomonoterpenic alkaloids vincristine and vinblastine. In this work we studied the biological potential of the roots, which are used in several countries as decocts or hot water extracts for the treatment of a number of conditions. The aqueous extract strongly inhibited acetylcholinesterase (AchE) in an in vitro microassay, an effect ascribable mainly to serpentine (IC(50) = 0.775 microM vs physostigmine IC(50) = 6.45 microM) as assessed with the pure compound. Pure alkaloids were tested for muscarinic and nicotinic antagonism using rat ex-vivo preparations, namely, ileum and diaphragm/phrenic-nerve, respectively. Serpentine competitively blocked muscarinic receptors with a pA(2) of 5.2, whereas the precursor ajmalicine up to 80 microM was undistinguishable from control, and catharanthine exhibited an unsurmountable muscarinic antagonism at greater than 10 microM concentrations. Nicotinic receptor mediated diaphragm contractions were fully inhibited by catharanthine (IC(50) = 59.6 microM) and ajmalicine (IC(50) = 72.3 microM), in a reversible but non-competitive manner, unlike the more potent nicotinic antagonist tubocurarine (IC(50) = 0.35 microM) whose competitive blockade was overcome by a physostigmine-induced increase in acetylcholine. Serpentine up to 100 microM did not change diaphragm contractions suggesting reduced affinity for neuromuscular nicotinic receptors. Despite strong in vitro AchE inhibition, serpentine failed to restore diaphragm contractions upon submaximal tubocurarine blockade, suggesting that poor tissue penetration may prevent serpentine from inhibiting AchE in deep neuromuscular synapses in the ex-vivo preparation. To our knowledge, the present study is the first to assess the effect of C. roseus root extracts, as well as of serpentine, ajmalicine and catharanthine on AchE. The results described herein suggest that the currently overlooked C. roseus roots may constitute a promising source of compounds with pharmaceutical interest. Moreover, given serpentines potent in vitro AchE inhibitory activity and low cholinergic receptor affinity, it is conceivable that minor structural modifications may yield a potent and selective AchE inhibitor, potentially useful for the pharmacological management of conditions such as Alzheimers disease and/or myasthenia gravis.
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Effects of an antagonist of the gastrin-releasing peptide receptor in an animal model of uveitis.
Invest. Ophthalmol. Vis. Sci.
PUBLISHED: 06-10-2009
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Some studies have shown the role of gastrin-releasing peptide (GRP) on the production and release of cytokines both in animal models and in humans with inflammatory diseases, but there are no reports on the effects of GRP in ocular inflammatory disease, mainly uveitis. The authors report on the effects of the GRP receptor (GRPR) antagonist RC-3095 in a well-established model for uveitis induced by the administration of lipopolysaccharide (LPS), comparing its effects with those of glucocorticoids.
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Simple and reproducible HPLC-DAD-ESI-MS/MS analysis of alkaloids in Catharanthus roseus roots.
J Pharm Biomed Anal
PUBLISHED: 05-22-2009
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Catharanthus roseus is one of the most important medicinal plants worldwide. The leaves of this species are the only source of the indolomonoterpenic alkaloids vincristin (leurocristine) and vinblastin (vincaleucoblastine), whose anticancer activity represents powerful therapeutics to many diseases, such as Hodgkin lymphoma. Usually, the remaining plant parts go to waste. Here we describe a phytochemical study on this species roots. Alkaloids in aqueous extracts, the usual form of consumption of this matrix, were studied using HPLC-DAD-ESI-MS/MS, which allowed the identification of 19-S-vindolinine, vindolinine, ajmalicine and an ajmalicine isomer, tabersonine, catharanthine, serpentine and a serpentine isomer. Quantification of the identified compounds revealed that serpentine and its isomer were predominant (64.7%) over the other alkaloids, namely vindolinine and its isomer (23.9%), catharanthine (7.7%) and ajmalicine (3.8%). The used procedure revealed to be simple, sensitive and reproducible.
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Boerhaavia diffusa: metabolite profiling of a medicinal plant from Nyctaginaceae.
Food Chem. Toxicol.
PUBLISHED: 05-06-2009
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Boerhaavia diffusa is a plant which is extensively used in folk medicine. However, when it comes to its phytochemical characterization, little attention has been given to secondary metabolites other than rotenoids and alkaloids. A metabolite profiling and biological study was undertaken in this species leaves and roots and substantial differences were found between the two parts of the plant. The volatile composition was analysed for the first time using HS-SPME-GC-MS and several compounds, including terpenes, phenylpropanoids, indol compounds, norisoprenoids, among others, were identified. Organic acid analysis was also performed, allowing their characterization in this species for the first time, and oxalic, ketoglutaric, pyruvic, quinic and fumaric acids were identified. Quantitative differences between the two vegetal materials were found. Additionally, several flavonoids and one phenolic acid were also confirmed. Concerning the biological potential, the aqueous extract of each plant part was tested against DPPH radical, one reactive oxygen species (O(2)(-)) and one reactive nitrogen species (()NO). Moreover, activity against acetylcholinesterase, an enzyme with a well-known role in several physio-pathological processes, was assayed. When possible, the relation between the chemistry and activity displayed was established. Leaves revealed stronger antioxidant activity than roots, and acetylcholinesterase inhibition was not found in neither plant part.
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Screening of antioxidant phenolic compounds produced by in vitro shoots of Brassica oleracea L. var. costata DC.
Comb. Chem. High Throughput Screen.
PUBLISHED: 03-12-2009
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The phenolic compounds produced by in vitro shoots of Brassica oleracea L. var. costata DC were screened by HPLC-DAD-MS/MS. Thirty seven compounds were characterized, which included chlorogenic acids, flavonoids (the majority of them were hydroxycinnamic acid esters of kaempferol and quercetin glycosides) and hydroxycinnamic acyl glycosides (with predominance of synapoyl gentiobiosides). The antioxidant capacity of the shoots was assessed against DPPH radical and two reactive oxygen species (superoxide radical and hypochlorous acid). A strong concentration-dependent antioxidative capacity was verified in the DPPH and superoxide radicals assays, but a reduced effect was noticed against hypochlorous acid. The results obtained indicate that the in vitro production of B. oleracea var. costata shoots can become important in the obtention of a noticeable dietary source of compounds with health protective potential.
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Targeted metabolite analysis of Catharanthus roseus and its biological potential.
Food Chem. Toxicol.
PUBLISHED: 03-05-2009
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Catharanthus roseus is nowadays one of the most studied medicinal plants. In this work, further knowledge on different parts of this species (leaves, stems, seeds and petals) was achieved, namely phenolics by HPLC-DAD and organic acids and amino acids by HPLC-UV. Also, the biological potential, expressed as acetylcholinesterase inhibitory activity was accessed and, in some parts, an acetylcholinesterase inhibitory capacity higher than 85% was found (IC(50) at 422, 442 and 2683 microg/mL in leaves, stems and petals, respectively). C. roseus aqueous extract revealed to be a rich source of phenolics, namely caffeoylquinic acids and flavonoids derivatives (up to 4127 mg/kg in stems, 4484 mg/kg in seeds, 8688 mg/kg in leaves and 41125 mg/kg in petals), organic acids (962, 6678, 25972 and 12463 mg/kg in seeds, petals, stems and leaves, respectively), such as citric acid (over 85% in some plant parts), and amino acids (31557, 39327, 50540 and 159697 mg/kg in stems, petals, seeds and leaves, respectively), of which arginine was a major compound.
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Pieris brassicae inhibits xanthine oxidase.
J. Agric. Food Chem.
PUBLISHED: 02-21-2009
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The antioxidant potential of an aqueous extract obtained from Pieris brassicae larvae reared on Brassica oleracea L. var. costata DC was evaluated against 2,2-diphenyl-1-picrylhydrazyl radical and several reactive oxygen species. The results revealed an effective concentration-dependent protective activity against superoxide and hydroxyl radicals, being superior to that of the host plant. In addition, the larvae extract also exhibited a strong inhibitory effect on xanthine oxidase that was not observed for B. oleracea var. costata. A weak scavenging ability was noticed for hypochlorous acid. Several phenolic compounds with complex chemical structures that are hard to synthesize in the laboratory were found in P. brassicae extract. This is the first time that an insect has been tested for its xanthine oxidase inhibitory capacity, which proved to be very high. These findings are interesting considering that they can be used by food or pharmaceutical industries to prevent the oxidation of their products, to increase the dietary supply of antioxidants, or for prevention of free radical-mediated diseases, namely, gout.
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In vitro cultures of Brassica oleracea L. var. costata DC: potential plant bioreactor for antioxidant phenolic compounds.
J. Agric. Food Chem.
PUBLISHED: 02-06-2009
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In this work were studied the phenolic composition of in vitro material (shoots, calli, and roots) of Brassica oleracea var. costata and its antioxidant capacity. Samples were obtained in different culture medium, with distinct supplementations to verify their influence on those parameters. Phenolic determination was achieved by HPLC-DAD. Antioxidant activity was assessed against DPPH. In calli and roots no phenolic compound was identified. In shoots was verified the presence of 36 compounds, which included hydroxycinnamic acids, flavonoids (kaempferol and quercetin derivatives), and hydroxycinnamic acyl glycosides (with a predominance of synapoyl gentiobiosides). MS liquid medium supplemented with 2 mg/L benzylaminopurine (BAP) and 0.1 mg/L naphthaleneacetic acid (NAA) revealed to be the best in vitro condition to produce shoot material with highest phenolic compound contents and stronger antioxidant potential, thus with a possible increase of health benefits.
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Volatile composition of Catharanthus roseus (L.) G. Don using solid-phase microextraction and gas chromatography/mass spectrometry.
J Pharm Biomed Anal
PUBLISHED: 02-03-2009
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A total of 88 volatile and semi-volatile components were formally or tentatively identified in flowers, leaves and stems of Catharanthus roseus (L.) G. Don (cv. Little Bright Eye), by headspace solid-phase microextraction (HS-SPME) and by dichloromethane extraction, combined with gas chromatography-mass spectrometry (GC-MS). These include some diterpenic compounds (manool and manoyl oxides), a sesquiterpen (alpha-bisabolol), and some pyridine, pyrazine, indol and carotenoid derivatives. Applying multivariate analysis (principal component analysis and agglomerative hierarchic cluster analysis) to the HS-SPME-GC-MS data, it was possible to characterize each part of the vegetal material using a relative small number of compounds. Hence, flowers were richer in terpenic molecules (including limonene), alpha-bisabolol, methyljasmonate, cis-jasmone, 2-phenylethanol, phenylacetaldehyde, trans-2-octenal, benzylic alcohol and 2-isobutyl-3-methoxypyrazine. Leaves can be characterized by the methyl and propyl esters of fatty acids, mono- and disaturated, trans-phytol, carotenoid derivative compounds, hydrofarnesylacetone, methylanthranilate, manool and epi-manool oxide, while stems have high levels of volatile aldehydes, such as hexanal, octanal, cis-2-nonenal, cis-2-decenal, cis, trans-2,6-nonadienal, trans, trans-2,4-decadienal and cis, trans-2,4-decadienal. Dichloromethane extraction allowed also the identification of some alkaloid-like compounds that were not detected by HS-SPME.
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Detection of traumatic arthrotomy of the knee using the saline solution load test.
J Bone Joint Surg Am
PUBLISHED: 01-06-2009
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The saline solution load test helps to determine if a wound extends into the knee joint. Little is known about the volume of injected intra-articular saline solution that is needed to effectively rule in or rule out a traumatic arthrotomy of the knee. The purpose of the present study was to determine the appropriate volume and needle location for the diagnosis of a traumatic knee arthrotomy and to assess the effect of associated variables, including knee circumference, body mass index, and sex.
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Targeted metabolite analysis and biological activity of Pieris brassicae fed with Brassica rapa var. rapa.
J. Agric. Food Chem.
PUBLISHED: 01-01-2009
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For the first time, an insect-plant system, Pieris brassicae fed with Brassica rapa var. rapa, was tested for its biological capacity, namely, antioxidant (DPPH*, *NO, and O(2)*- radicals) and antimicrobial (bacteria and fungi) activities. Samples from the insects life cycle (larvae, excrements, exuviae, and butterfly) were always found to be more efficient than the host plant. Also, P. brassicae materials, as well as its host plant, were screened for phenolics and organic acids. The host plant revealed higher amounts of both compounds. Two phenolic acids, ferulic and sinapic, as well as kaempferol 3-Osophoroside, were common to insect (larvae and excrements) and plant materials, with excrements being considerably richer. Detection of sulfated compounds in excrements, absent in host plant, revealed that metabolic processes in this species involved sulfation. Additionally, deacylation and deglycosilation were observed. All matrices presented the same organic acids qualitative profile, with the exception of excrements.
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Cartilaginous choristoma of the tongue with an immunohistochemical study.
BMJ Case Rep
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By definition, choristomas are normal tissues found in anomalous topography. The cartilaginous features of these lesions are rare in the soft tissues of the oral cavity. The majority of cartilaginous choristomas of the tongue--the primary site of emergence of the oropharynx--are associated with adipose, fibrous or bone tissues--apart from that, only a few of these were confirmed by an immunohistochemical study. The neoplasm exclusively composed of chondromatous tissue is extremely rare in the tongue. This paper reports the clinical, surgical and pathological characteristics of a cartilaginous choristoma of the tongue diagnosed in a 64-year-old woman.
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A gas chromatography-mass spectrometry multi-target method for the simultaneous analysis of three classes of metabolites in marine organisms.
Talanta
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In this work a fast and simple multi-target gas chromatography-mass spectrometry (GC-MS) method for the simultaneous detection and absolute quantification of amino acids, fatty acids, sterols and lupanes in marine organisms is proposed. The methodology was applied to the characterization of the echinoderm Marthasterias glacialis Linnaeus spiny sea star extracts. The main factors influencing the extraction of target compounds were evaluated by using different extraction procedures, solvent systems and temperature conditions and a comparison with a reference technique was performed. The most suitable procedure, capable of successfully extract the three classes of target compounds, was ethanol as solvent at 40°C under magnetic stirring. Good analytical parameters were obtained since calibrations curves for the 40 compounds under analysis (15 amino acids, 16 fatty acids, 6 sterols and 3 lupanes) showed regression coefficients (r(2)) ranging from 0.9844 to 0.9978, with low RSD (from 0.00 to 9.45%), and detection limits varying from 0.03 to 15.40 ?g/L. The RSD values for intra- and interday variations studies were also good (RSD<13.5%, for both) and recoveries were higher than 92%. Variation in samples from different harvests and origins and their chemical composition during the year is reported. The fact that no previous treatment of samples is required can make this a useful technique for metabolite profiling in marine organisms, among others, both in biomedical and nutritional studies. Moreover, due to the fast and robust character of the proposed method it seems to be suitable for the implementation as routine analysis.
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Further insights on the carotenoid profile of the echinoderm Marthasterias glacialis L.
Mar Drugs
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In this study, the carotenoid profile of the echinoderm Marthasterias glacialis L. was established using HPLC-DAD-APCI-MS/MS equipped with a C(30) column. This approach rendered the identification of 20 compounds, eight of them reported for the first time in this marine organism. Differentiation of carotenoid isomers was also achieved.
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Comparison of ozone and chlorine in low concentrations as sanitizing agents of chicken carcasses in the water immersion chiller.
J. Food Prot.
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The aim of this study was to investigate the effects of the use of chlorine or ozone as sanitizing agents in the water of chicken immersion chilling, using the residual levels usually applied in Brazil (1.5 ppm), comparing the effects of these treatments on the microbiological, physicochemical, and sensory characteristics of carcasses. Chicken carcasses were chilled in water (4°C) with similar residual levels of ozone and chlorine until reaching temperatures below 7°C (around 45 min). The stability of carcasses was assessed during 15 days of storage at 2 ± 1°C. Microbiological, surface color (L*, a*, b* parameters), pH value, lipid oxidation (thiobarbituric acid reactive substances index), and sensory evaluation (on a 9-point hedonic scale for odor and appearance) analyses were carried out. The presence of Salmonella was not detected, coagulase-positive staphylococci counts were below 10(2) CFU/ml of rinse fluid, and Escherichia coli and total coliform counts were below 10(5) CFU/ml of rinse fluid until the end of the storage period for both treatments. Psychrotrophic microorganism counts did not differ (P > 0.05) between chlorine and ozone treatments, and both values were near 10(9) CFU/ml of rinse fluid after 15 days at 4 ± 1°C. pH values did not differ between treatments (P > 0.05) or during the storage period (P > 0.05). In addition, neither chlorine nor ozone treatment showed differences (P > 0.05) in the lipid oxidation of carcasses; however, the thiobarbituric acid reactive substances index of both treatments increased (P ? 0.05) during the storage period, reaching values of approximately 0.68 mg of malonaldehyde per kg. Samples from both treatments did not differ (P > 0.05) in their acceptance scores for odor and overall appearance, but in the evaluation of color, ozone showed an acceptance score significantly higher (P ? 0.05) than that for the chlorine treatment. In general, under the conditions tested, ozone showed results similar to the results for chlorine in the disinfection of chicken carcasses in the immersion chilling, which may indicate its use as a substitute for chlorine in poultry slaughterhouses.
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Biological Effect of Leaf Aqueous Extract of Caesalpinia pyramidalis in Goats Naturally Infected with Gastrointestinal Nematodes.
Evid Based Complement Alternat Med
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Forty-eight goats naturally infected with gastrointestinal nematodes were randomly divided into four groups (n = 12): negative control (G1) (untreated), positive control (G2) (treated with doramectin, 1?mL/50?Kg b.w.), and G3 and G4 treated with 2.5 and 5?mg/Kg b.w. of a leaf aqueous extract of Caesalpinia pyramidalis (CP). Fecal and blood samples were regularly collected for the evaluation of fecal egg count (FEC), hematological and immunological parameters to assess the anthelmintic activity. In treated animals with CP, there was noted a significant reduction of 54.6 and 71.2% in the mean FEC (P < 0.05). An increase in IgA levels was observed in G3 and G4 (P < 0.05), during the experimental period, suggesting that it was stimulated by the extract administration. In conclusion, the results showed that CP provoked a protective response in infected animals treated with them. This response could be partly explained by the CP chemical composition.
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GC-MS Lipidomic Profiling of the Echinoderm Marthasterias glacialis and Screening for Activity against Human Cancer and Non-cancer Cell Lines.
Comb. Chem. High Throughput Screen.
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Marine organisms have been increasingly regarded as an excellent source of bioactive molecules for human health. As part of an on-going study to elucidate the chemical composition and biological activity of this organism, we report here the lipidomic profile of this organism and screening for anticancer activity. Two classes of biologically active metabolites were identified and quantified by a GC-MS optimized method for screening several classes of metabolites in a single run. Free fatty acids and sterols were found, including ergosterol, ?-sitosterol and cholesterol derivatives, some of which are reported in this species for the first time. Distinct assays were performed to screen extracts effect on viability, membrane integrity and density of three human cancer cell lines: human oestrogen receptor-positive (ER+) breast cancer (MCF-7), human neuroblastoma (SH-SY5Y) and human colon cancer (Caco-2). Differential activity towards the three cancer cell lines was found, SH-SY5Y cell line being the most susceptible. No activity was found for Caco-2 cell line. Non-cancer cell lines (human dermal fibroblasts and human foreskin fibroblasts) were also tested and revealed to be less susceptible. This work establishes M. glacialis as a potential source of bioactive molecules for further studies.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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